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Anabolic steroid abuse has also been associated with psychiatric disorders and increased use of intoxicants.1 However, it is important in studies using these and other substance abuse outcomes to examine the influence of other factors, with a focus on the underlying biological mechanisms. A number of genetic variants, associated with various aspects of the brain, have been associated with abuse of different drugs that can be potentially pharmacologically abused, including alcohol, nicotine, prescription drugs and drugs commonly consumed both on a recreational level and in the workplace.2,3 This has led to the development of various drugs for the treatment of substance abuse and misuse, and to the development of novel drugs to treat addictive behaviours. One of these drugs on the market is Naltrexone,4 which targets neuronal nitric oxide synthase. Nitric oxide synthase (NOS) is a major enzyme for the production of dopamine, which is considered to be the central neurotransmitter for many neuropsychiatric disorders. NOS is located in the nucleus accumbens, an area in the brain known for the rewarding aspect of drug action. It is thought that the NOS is required for the induction of a positive reward effect due to dopamine in the rewarding pathways (for example, during reinforcement), and for tolerance as demonstrated in experiments using rats.5,6 The effect of NOS treatment in humans for reducing drug-seeking behaviour in response to drugs, such as amphetamine and cocaine, has been shown in a controlled study at 10 weeks of therapy.7For example, NOS inhibitors are currently being used for chronic non-cancer pain. They enhance acetylcholine secretion and enhance opioid-like effects. Furthermore, NOS inhibitors reduce the rewarding potential of stimulant drugs of abuse, such as caffeine, but they do not affect their addictive properties.8,9 Another NOS inhibitor known as MK-12, which increases NOS activity in the brain, has previously shown no effect on the rewarding properties of drugs of abuse. 10 However, in another reported study, NOS inhibitors, which block the activity of NOS, decreased cocaine self-administration.11 Such studies highlight the importance of NOS involvement in both the reinforcing effects of drug use, as well as in the tolerance that may result.12 A study using functional MRI, which included functional brain imaging, found that the nucleus accumbens, where NOS is located, was differentially affected by acute and chronic administration of MDMA.13 In this study, it was found that MDMA increased activity and increased activation of nucleus accumbens areas associated with reward and reward-related behaviours, whereas NOS decreased activitySimilar articles: